The overall objective of this proposal is to delineate the mechanism(s) by which the body repletes muscle glycogen and other fuel reservoirs following exercise. Observations obtained with a perfused hindquarter preparation, in large part in our laboratory, have suggested that (1) Following exercise there are two phases of glycogen repletion; phase I in which enhanced glucose utilization and glycogen synthesis are demonstrable in the absence of insulin and phase II in which these processes are enhanced due to increased insulin sensitivity; and (2) The increases in glucose utilization and glycogen synthesis in both phases occur predominantly in muscles which performed work (were deglycogenated) during the exercise. We propose to utilize a number of experimental models including the perfused rat hindquarter, the incubated soleus muscle and the intact rat to determine the basis for these findings and to explore their physiological implications. The following hypotheses will be tested: (1) Phase I and phase II alterations in glucose metabolism following exercise are part of a continuum of metabolic events which result in the restoration of tissue fuel reservoirs. We will attempt to provide that phase I occurs immediately after exercise and is associated with the initially rapid rate of muscle glycogen repletion, whereas phase II occurs later and is associated with the phenomenon of supercompensation. We will also attempt to show that processes other than glucose metabolism and tissues other than muscle are correspondingly involved. (2) Increases in glucose utilization and glycogen synthesis in both phase I and phase II are due to local rather than systemic factors. The factors which we will study include: the bradykinin-prostaglandin system, insulin binding, regional blood flow and adenosine. (3) The increases in glucose transport in both phases are due to the same mechanism. In the course of these studies we will also investigate the mechanism by which muscle enhances glycogen synthesis following exercise and we will explore the possibility that changes in insulin sensitivity regulate the repletion of fuel reservoirs in other tissues. Finally, we will attempt to delineate the basis for some of the reported effects of prior exercise on glucose homeostasis.